POS0959 PERSISTENCE ON TREATMENT AND SAFETY OF TNF-ALPHA INHIBITORS BIOSIMILARS COMPARED TO ORIGINATORS: AN OBSERVATIONAL STUDY ON THE FRENCH NATIONAL HEALTH DATA SYSTEM
Authors: H. Jourdain, L. Hoisnard, E. Sbidian, M. Zureik
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Anti TNF-alpha drugs have revolutionized the management of immune-mediated inflammatory diseases (IMIDs). Since 2015, several biosimilar products have been marketed and reimbursed after the expiry of the originator patents of infliximab (IFX), etanercept (ETA) and adalimumab (ADA), reducing the cost of these treatments. Equivalence, i.e. efficacy and safety, between biosimilar and originator products is generally demonstrated in a randomised phase 3 trial in one indication, and then extrapolated to other indications. <h3>Objectives</h3> To compare the persistence and assess the safety profile of biosimilar products compared to originator product of IFX, ETA, and ADA in treatment initiators in all the licensed indications. <h3>Methods</h3> We used data from the French National Health Data System to identify IFX, ETA and ADA initiators from the date of marketing in France of the first biosimilar of each molecule (01/2015, 05/2016 and 10/2018 respectively) and until 30 June 2021. Patients were then followed during one year. Treatment persistence was defined as the duration without treatment discontinuation (60 days gap plus theoretical coverage of the molecule without treatment delivery) or modification (for another biologic treatment), censoring the follow-up at 1 year of follow-up, death or intra-molecule switch (for at least 2 consecutive deliveries). Persistence was compared between users of the originator product and biosimilars by Cox regressions and comparison of cumulative risks of event using Kaplan Meier survival probabilities at 1 year, weighting the populations on the inverse probability of treatment. Analyses were performed by molecule, by disease treated and by biosimilar product used. Adverse treatment events, including infections, majors cardiovascular events, immunology disorders, cancers, death and all-cause hospitalization, were also described by comparing originator and biosimilar event rates. Various sensitivity analyses were carried out: 2-year follow-up, gap modification for discontinuation definition, intra-molecule switch defined as at least 3 consecutive deliveries of another product, restricting the analysis to at least 6-month persistent patients, and classifying the biosimilar to originator switch as an outcome and not a censoring event. <h3>Results</h3> A total of 86,776 patients were included in the study (22,670, 24,442 and 39,664 IFX, ETA and ADA initiators respectively). Within molecules, subject characteristics at inclusion were very similar between originator and biosimilar products. After weighting, the hazard ratios (HR) and relative risks of treatment discontinuation or modification in biosimilar versus originator products were close to 1 or below 1, with confidence intervals covering 1, except for ADA ABP501 which showed a minor increased risk of non-persistence compared to ADA originator in inflammatory bowel diseases (HR 1.24 [1.09-1.41] and 1.22 [1.03-1.44] in CD and UC). Crude adverse event rates were very similar between biosimilars and originator products. All sensitivity analyses were consistent with the main results. <h3>Conclusion</h3> Our study shows reassuring results regarding the persistence and safety of biosimilars compared to the originator anti-TNF alpha product in all licensed indications. Further studies need to be carried out to confirm these results, and to investigate the switch context. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.